Phosphodiesterase7 Inhibition Activates Adult Neurogenesis in Hippocampus and Subventricular Zone in vitro and in vivo
Jose A. Morales-Garcia, Victor Echeverry-Alzate, Sandra Alonso-Gil, Marina Sanz-SanCristobal, Jose A. Lopez-Moreno, Carmen Gil, Ana Martinez, Angel Santos and Ana Perez-Castillo
Accepted manuscript online: 19 AUG 2016 04:52AM EST | DOI: 10.1002/stem.2480
The phosphodiesterase 7 (PDE7) enzyme is one of the enzymes responsible for controlling intracellular levels of cAMP in central nervous system. Here we described that PDE7 inhibition controls, in vitro and in animal models, stem cell expansion in the two main adult neurogenic niches: the subgranular zone of the dentate gyrus of the hippocampus (SGZ) and the subventricular zone (SVZ) in the adult rat brain. Adult rats orally treated with an inhibitor of PDE7, presented in the SGZ and the SVZ elevated numbers of proliferating progenitor cells, migrating precursors and finally a significant increase in newly generated neurons in the olfactory bulb and the hippocampus together with a better performance in memory tests. Our results indicate for the first time that inhibition of PDE7 directly regulates proliferation, migration and differentiation of neural stem cells, improving spatial learning and memory tasks.